Potten C S
CRC Department of Epithelial Biology, Paterson Institute for Cancer Research, Christie Hospital (NHS) Trust, Manchester, UK.
Int J Cancer. 1995 Jul 28;62(3):356-61. doi: 10.1002/ijc.2910620321.
The rapidly proliferating gastrointestinal mucosa is one of the major limiting tissues in cancer therapy. Because of its short transit time and high sensitivity to radiation and chemotherapeutic drugs, damage is rapidly manifested. Protection of the important stem cells in the tissue could be achieved, in principle, by appropriate prior manipulation with cytokines or growth factors which might make them more resistant to the cytotoxic treatment, for example, by putting them out of cycle. Such strategies might reduce some of the adverse side-effects of cancer treatment and improve the quality of life of patients, while possibly allowing an escalation of therapeutic dose. The functional capacity of stem cells has been studied for many years using a microcolony assay technique which measures the regenerative capacity of the clonogenic stem cells in crypts. These cells determine the survival of crypts which themselves determine whether or not the mucosal integrity is maintained and ultimately whether the animal or patient survives. Here, we demonstrate that treatment with interleukin-11 for 2 days prior to radiation exposure can significantly increase the number of surviving crypts. Treatment with IL-11 both before (for 2 days) and after irradiation (for 3 days) produces a slightly enhanced protection. Up to about 4 times more crypts survive at the highest radiation dose after either of these treatment schedules. These studies may provide a radiobiological explanation for the increased survival of animals when IL-11 is administered during 5FU and radiation exposures.
快速增殖的胃肠道黏膜是癌症治疗中的主要限制组织之一。由于其转运时间短且对辐射和化疗药物高度敏感，损伤会迅速显现。原则上，通过事先用细胞因子或生长因子进行适当处理，使组织中的重要干细胞更能抵抗细胞毒性治疗，例如使它们脱离细胞周期，就可以实现对干细胞的保护。这类策略可能会减少癌症治疗的一些不良副作用，提高患者的生活质量，同时有可能允许提高治疗剂量。多年来一直使用微集落测定技术研究干细胞的功能能力，该技术可测量隐窝中克隆形成干细胞的再生能力。这些细胞决定隐窝的存活，而隐窝本身决定黏膜完整性是否得以维持，最终决定动物或患者能否存活。在此，我们证明在辐射暴露前用白细胞介素-11处理2天可显著增加存活隐窝的数量。在照射前（2天）和照射后（3天）都用IL-11处理可产生稍强的保护作用。在这两种治疗方案中的任何一种之后，在最高辐射剂量下存活的隐窝数量最多可增加约4倍。这些研究可能为在5-氟尿嘧啶和辐射暴露期间给予IL-11时动物存活率提高提供放射生物学解释。
